Mild organic ammonium tribromide-mediated regioselective ring opening of epoxides with alcohols, water, acetic anhydride, and amines under solvent-free reaction conditions

Article abstract of DOI:10.1080/00397911.2010.493259

Organic ammonium tribromide (OATB), N-methylpyrrolidine-2-one hydrotribromide (MPHT) was found to be an efficient catalyst for the regioselective ring opening of epoxides with various nucleophiles under solvent free conditions. This procedure occurs under neutral and mild reaction conditions with out adding any additive and afforded high yields of products.

Full text of DOI:10.1080/00397911.2010.493259

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Mild Organic Ammonium
Tribromide–Mediated Regioselective
Ring Opening of Epoxides with Alcohols,
Water, Acetic Anhydride, and Amines
Under Solvent-Free Reaction Conditions
Sweety Singhal a , Suman L. Jain a & Bir Sain a
a Chemical Sciences Division , Indian Institute of Petroleum, Council
of Scientific and Industrial Research , Dehradun , India
Published online: 29 Apr 2011.
To cite this article: Sweety Singhal , Suman L. Jain & Bir Sain (2011) Mild Organic Ammonium
Tribromide–Mediated Regioselective Ring Opening of Epoxides with Alcohols, Water, Acetic
Anhydride, and Amines Under Solvent-Free Reaction Conditions, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 41:12, 1829-1837,
DOI: 10.1080/00397911.2010.493259
To link to this article: http://dx.doi.org/10.1080/00397911.2010.493259
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Synthetic Communications1, 41: 1829–1837, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.493259
MILD ORGANIC AMMONIUM TRIBROMIDE–MEDIATED
REGIOSELECTIVE RING OPENING OF EPOXIDES WITH
ALCOHOLS, WATER, ACETIC ANHYDRIDE, AND
AMINES UNDER SOLVENT-FREE REACTION
CONDITIONS
Sweety Singhal, Suman L. Jain, and Bir Sain
Chemical Sciences Division, Indian Institute of Petroleum, Council of
Scientific and Industrial Research, Dehradun, India
GRAPHICAL ABSTRACT
Abstract Organic ammonium tribromide (OATB), N-methylpyrrolidine-2-one hydrotribro-
mide (MPHT) was found to be an efficient catalyst for the regioselective ring opening of
epoxides with various nucleophiles under solvent free conditions. This procedure occurs
under neutral and mild reaction conditions with out adding any additive and afforded high
yields of products.
Keywords Metal free; MPHT; regioselective synthesis; ring opening; solid bromine
INTRODUCTION
Ring opening of epoxides with nucleophilic reagents is an important synthetic
transformation as it offers a simple and straightforward approach for the synthesis
of several regio- and stereoselective 1,2-difunctionalized ring-opened products.[1,2]
The commonly used methods for the ring opening of epoxides with nucleophiles
involve the use of strong acids or bases,[3,4] which have several limitations such as
formation of undesirable side products mainly due to di- or polymerization of epox-
ides, lesser yields, and extended reaction times. Subsequently, several improved cata-
lytic methodologies mainly using transition metal–based or metal-free catalysts
under homogeneous or heterogeneous conditions have been developed for this
Received February 1, 2010.
Address correspondence to Suman L. Jain, Chemical Sciences Division, Indian Institute of
Petroleum, Council of Scientific and Industrial Research, Dehradun 248005, India. E-mail: suman@
iip.res.in
1829

1830
S. SINGHAL, S. L. JAIN, AND B. SAIN
Scheme 1. Regioselective ring opening of epoxides.
transformation.[5–10] Although these methods generally lead to high yields with good
regioselectivity, the use of toxic=expensive transition metals restrict their widespread
applicability. In recent years, use of transition metal–free catalytic systems has
become desirable, particularly for the preparation of compounds that do not tolerate
metal contamination such as pharmaceuticals.
Organic ammonium tribromides (OATB),[11,12] also referred to as solid bro-
mines because of their crystalline nature, ease of synthesis=handling, better storage
stability, and capacity to maintain the desired stoichiometry, have proven to be safer
and promising alternatives to toxic molecular bromine and anhydrous HBr in
organic reactions. The use of these compounds for bromination of organic com-
pounds is well documented, but little is known about their catalytic potential for
organic transformations.
In the present article, we report a simple methodology for the regioselective
ring opening of epoxides with various nucleophiles such as alcohols, water, acetic
anhydride, and amines to afford corresponding b-alkoxy alcohols, 1,2-diols, 1,2-
diacetates, and b-amino alcohols in the presence of a catalytic amount of
N-methylpyrrolidine-2-one hydrotribromide (MPHT)[13] without adding any
additive under solvent-free conditions (Scheme 1).
RESULTS AND DISCUSSION
Initially, we studied the nucleophilic ring opening of various epoxides with
equimolar amounts of MPHT (1:1.2) in acetonitrile at room temperature. These
results are presented in Table 1. All the epoxides smoothly underwent regioselective

RING OPENING OF EPOXIDES
1831
Table 1. Ring opening of epoxides with MPHT in acetonitrilea
Entry
1
Epoxide 1
Product 2
Yield (%)b
98
2
3
94
95
4
5
96
94
6
7
98
98
aReaction conditions: epoxide (1 mmol), MPHT (1.2 mmol), acetonitrile (3 ml); reaction time 15–20 min
at room temperature.
bIsolated yields.
ring opening and afforded b-bromohydrins selectively without any evidence of the
formation of by-products. 2-Arylepoxides, for example, styrene oxide, underwent
regioselective ring cleavage with the preferential attack at the benzylic position,
probably because of formation of stabilized benzylic cation as a reactive intermedi-
ate during the reaction (Table 1, entries 1–3). In the case of 2-alkyl epoxides,
ring-opening products were formed by cleavage at the terminal position with the
preferential attack of nucleophile from the less-hindered side (Table 1, entries 4
and 5). Cycloalky epoxides such as cyclohexane epoxide and cyclopentane epoxide
were efficiently reacted with MPHT and yielded the corresponding 2-bromo cyclo-
hexanol and 2-bromocyclopentanol respectively in good yields (Table 1, entries 6
and 7). Further, we studied the regioselective ring opening of epoxides with alcohols,
acetic anhydride, amines, and water in the presence of a catalytic amount of MPHT
under solvent-free condition (Scheme 1). A variety of epoxides reacted smoothly

1832
S. SINGHAL, S. L. JAIN, AND B. SAIN
Table 2. MPHT-catalyzed ring opening of epoxides with alcohols, water, and acetic anhydridea
Entry
1
Epoxide 1
Nucleophile
MeOH
Product 3, 4, 5
Time (h) Yield (%)b
1.0
3.5
96
75
2
3
PhCH2OH
1.5
90
4
5
2.5
1.5
85
92
MeOH
6
7
8
MeOH
MeOH
2.0
1.5
2.5
94
89
80
9
MeOH
MeOH
2.0
3.0
84
92
10
11
1.5
89
(Continued )

RING OPENING OF EPOXIDES
1833
Table 2. Continued
Entry
12
Epoxide 1
Nucleophile
Product 3, 4, 5
Time (h) Yield (%)b
MeOH
1.0
1.0
93
87
13
14
H2O
1.0
1.5
97
97
15
Ac2O
16
17
H2O
2.0
2.0
94
92
Ac2O
18
H2O
1.5
97
19
20
21
Ac2O
H2O
1.5
1.5
1.5
97
97
97
Ac2O
aReaction conditions: Epoxide (1 mmol), nucleophile (2 mmol), and MPHT (10 mol%) at room
temperature.
bIsolated yields.
with various alcohols such as benzylic, primary, secondary, and tertiary in the pres-
ence of a catalytic amount of MPHT and yielded corresponding b-hydroxy ethers in
good yields as shown in Table 2. Again, aryl epoxides underwent ring opening at the
benzylic position regioselectively (Table 2, entries 1–4), whereas alkyepoxides such as
epichlorhydrin and heptane oxide gave ring-opened products by cleavage at the ter-
minal position because of the preferential attack of the nucleophile from the
less-hindered side (Table 2, entries 7–9). However, the hydrolysis of epoxides in

1834
S. SINGHAL, S. L. JAIN, AND B. SAIN
Table 3. MPHT-catalyzed ring cleavage of epoxides with aminesa
Entry
Epoxide 1
Amine
Product 6
Time (h)
Yield (%)b
1
2.5
80
2
3.0
80
3
5.0
72
55
4
5
CH3CH2CH2NH2
8.0
3.0
80
65
6
7
5.0
5.0
70
(Continued )

RING OPENING OF EPOXIDES
1835
Table 3. Continued
Entry
Epoxide 1
Amine
Product 6
Time (h)
Yield (%)b
8
5.0
75
aReaction conditions: Epoxide (1mmol), amine (2.0mmol), MPHT and (10 mol%) at room temperature.
bIsolated yields.
the presence of a catalytic amount of MPHT yielded corresponding vic-diols selec-
tively in excellent yields under the described reaction conditions (Table 2, entries
14, 16, 18, and 20). Similarly, ring cleavage of epoxides in acetic anhydride using
MPHT as catalyst yielded exclusively 1,2-diacetates in good yields (Table 2, entries
15, 17, 19, and 21).
To extent that the catalytic potential of the protocol developed, we studied the
ring cleavage of styrene oxide with various aromatic and aliphatic amines by using
MPHT as catalyst under similar reaction conditions. These results are presented in
Table 3 (entry 1–4). All the reactions were found to be regioselective and yielded cor-
responding b-hydroxy amines by cleavage on the benzylic position. Alkyl amines in
general were found to be less reactive than anilines in terms of the reaction times and
yields of the cleaved product. Next we carried out the ring opening of various epox-
ides with aniline under the described reaction conditions (Table 3).
In summary, we have described the use of the MPHT, an easily accessible
organic ammonium tribromide, as a stoichiometric reagent or catalyst for the ring
opening of various epoxides with a number of nucleophiles under mild reaction
conditions. MPHT can be considered to be a versatile reagent that has remarkable
stability and does not decompose on storage at room temperature even after a long
time. It is not corrosive and can easily be handled because of its crystalline nature.
Furthermore, the use of solvent-free conditions makes this process more advan-
tageous from environmental viewpoints.
EXPERIMENTAL
General Procedure for Ring Opening of Epoxides with MPHT
in Acetonitrile
MPHT (1.2 mmol) was added to a stirred solution of an epoxide (1 mmol) in dry
acetonitrile (3 ml), and the reaction was continued at room temperature for 15–20 min.
After completion of the reaction, the solvent was evaporated under reduced pressure.
The residue thus obtained was dissolved in dichloromethane and extracted with water
(3 Â 10 ml). The combined organic layer was dried over anhydrous Na2SO4 and con-
centrated under vacuum. The crude product was purified by flash chromatography
using EtOAc=hexane (1:9) as eluent to afford pure b-bromohydrin. All the products
were characterized by their physical and spectral analysis.

1836
S. SINGHAL, S. L. JAIN, AND B. SAIN
General Procedure for MPHT-Catalyzed Nucleophilic Ring Opening
with Alcohols, Water, Acetic Anhydride, and Amines
Nucleophile (2 mmol) was added into a stirred mixture of an epoxide (1 mmol)
and MPHT (10 mol%) in a 50-ml round-bottomed flask, and the reaction continued
at room temperature for the appropriate time as mentioned in Tables 2 and 3. After
completion of the reaction as indicated by thin-layer chromatography (TLC), the
reaction mixture was quenched with water and extracted with dichloromethane
(3 Â 10 ml). The combined organic layer was dried over anhydrous Na2SO4 and con-
centrated under vacuum. The crude product was purified by flash chromatography
to yield pure b-hydroxy product.
ACKNOWLEDGMENTS
We are grateful to the director, Indian Institute of Petroleum, for his kind
permission to publish these results. S. L. J. and S. S. are thankful to the Council
of Scientific and Industrial Research New Delhi, for the award of research
fellowships.
REFERENCES
1. Parker, R. E.; Isaacs, N. S. Mechanisms of epoxide reactions. Chem. Rev. 1959, 59,
737–799.
2. Bonini, C.; Righi, G. Regio- and chemoselective synthesis of halo-hydrins by cleavage of
oxiranes with metal halides. Synthesis 1994, 225–238.
3. Yadav, J. S.; Ramesh Reddya, A.; Venkat Narsaiaha, A.; Reddy, B. V. S. An efficient
protocol for regioselective ring opening of epoxides using samarium triflate: Synthesis
of propranolol, atenolol, and RO363. J. Mol. Catal. A: Chem. 2007, 261, 207–212.
4. Das, B.; Reddy, V. S.; Tehseen, F. A mild, rapid, and highly regioselective ring-opening of
epoxides and aziridines with acetic anhydride under solvent-free conditions using
ammonium-12-molybdophosphate. Tetrahedron Lett. 2006, 47, 6865–6868.
5. Yadav, J. S.; Reddy, B. V. S.; Harikishan, K.; Narsaiah, M. A. V. Carbon tetrabromide:
An efficient catalyst for regioselective ring opening of epoxides with alcohols and water.
Synthesis 2005, 2897–2890, and references cited therein.
6. Iranpoor, N.; Salehi, P. Highly efficient regio- and stereoselective alcoholysis of epoxides
catalyzed with iron(III) chloride. Synthesis 1994, 1152–1154.
7. Salehi, P.; Dabiri, M.; Zolfigol, M. A.; Fard, M. A. B. Silica sulfuric acid: An efficient and
reusable catalyst for regioselective ring opening of epoxides by alcohols and water.
Phosphorus, Sulfur Silicon Relat. Elem. 2004, 179, 1113–1121.
8. Firouzabadi, H.; Iranpoor, N.; Khoshnood, A. Aluminum tris (dodecyl sulfate) trihydrate
Al(DS)3 Á 3H2O as an efficient Lewis acid–surfactant combined catalyst for organic reac-
tions in water: Efficient conversion of epoxides to thiiranes and to amino alcohols at room
temperature. J. Mol. Catal A: Chem. 2007, 274, 109–115.
9. Vijender, M.; Kishore, P.; Narender, P.; Satyanarayana, B. Amberlist-15 as heterogeneous
reusable catalyst for regioselective ring opening of epoxides with amines under mild
conditions. J. Mol. Catal. A: Chem. 2007, 266, 290–293.
10. Kamal, A.; Ramu, R.; Azhar, M. A.; Khanna, G. B. R. Copper(II) tetrafluoroborate–
catalyzed ring opening of epoxides by amines. Tetrahedron Lett. 2005, 46, 2675–2677.

RING OPENING OF EPOXIDES
1837
11. Mondal, E.; Sahu, P. R.; Bose, G.; Khan, A. T. A useful and convenient synthetic proto-
col for interconversion of carbonyl compounds to the corresponding 1,3-oxathiolanes and
vice versa employing organic ammonium tribromide (OATB). Tetrahedron Lett. 2002, 43,
2843–2846.
12. Chaudhuri, M. K.; Khan, A. T.; Patel, B. K.; Dey, D.; Khramawphlang, W.;
Lakshmiprabha, T. R.; Mandal, G. C. An environmentally benign synthesis of organic
ammonium tribromide (OATB) and bromination of selected organic substrates by tetra-
butylammonium tribromide (TBATB). Tetrahedron Lett. 1998, 39, 8163–8166.
13. Bekaert, A.; Provot, O.; Rasolojaona, O.; Alami, M.; Brion, J. D. N-Methylpyrrolidin-
2-one hydrotribromide (MPHT), a mild reagent for selective bromination of carbonyl
compounds: Synthesis of substituted 2-bromo-1-naphtols. Tetrahedron Lett. 2005, 46,
4187–4191.